Document Detail


Overexpression of the dynein light chain km23-1 in human ovarian carcinoma cells inhibits tumor formation in vivo and causes mitotic delay at prometaphase/metaphase.
MedLine Citation:
PMID:  21469138     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
km23-1 is a dynein light chain that was identified as a TGFβ receptor-interacting protein. To investigate whether km23-1 controls human ovarian carcinoma cell (HOCC) growth, we established a tet-off inducible expression system in SKOV-3 cells in which the expression of km23-1 is induced upon doxycycline removal. We found that forced expression of km23-1 inhibited both anchorage-dependent and anchorage-independent growth of SKOV-3 cells. More importantly, induction of km23-1 expression substantially reduced the tumorigenicity of SKOV-3 cells in a xenograft model in vivo. Fluorescence-activated cell sorting analysis of SKOV-3 and IGROV-1 HOCCs demonstrated that the cells were accumulating at G2/M. Phospho-MEK, phospho-ERK and cyclin B1 were elevated, as was the mitotic index, suggesting that km23-1 suppresses HOCCs growth by inducing a mitotic delay. Immunofluorescence analyses demonstrated that the cells were accumulating at prometaphase/metaphase with increases in multipolar and multinucleated cells. Further, although the mitotic spindle assembly checkpoint protein BubR1 was present at the prometaphase kinetochore in Dox+/- cells, it was inappropriately retained at the metaphase kinetochore in Dox- cells. Thus, the mechanism by which high levels of km23-1 suppress ovarian carcinoma growth in vitro and inhibit ovary tumor formation in vivo appears to involve a BubR1-related mitotic delay.
Authors:
Nageswara R Pulipati; Qunyan Jin; Xin Liu; Baodong Sun; Manoj K Pandey; Jonathan P Huber; Wei Ding; Kathleen M Mulder
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Publication Detail:
Type:  Journal Article     Date:  2011-04-25
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  129     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-05-27     Completed Date:  2011-07-27     Revised Date:  2014-09-12    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  553-64     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 UICC.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Division
Cell Line, Tumor
Cytoplasmic Dyneins / metabolism*
Dyneins / metabolism*
Female
Humans
Metaphase
Mice
Mice, Nude
Mitosis
Neoplasm Transplantation
Ovarian Neoplasms / metabolism*,  prevention & control
Prometaphase*
Transplantation, Heterologous
Up-Regulation
Grant Support
ID/Acronym/Agency:
R01 CA090765/CA/NCI NIH HHS; R01 CA090765-10/CA/NCI NIH HHS; R01 CA092889/CA/NCI NIH HHS; R01 CA092889-08S1/CA/NCI NIH HHS; R01 CA092889-10/CA/NCI NIH HHS; R01 CA100239/CA/NCI NIH HHS; R01 CA100239-05/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/DYNLRB1 protein, human; EC 3.6.4.2/Cytoplasmic Dyneins; EC 3.6.4.2/Dyneins
Comments/Corrections

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